MRI is a proven non-invasive technique that makes high resolution image of the brain. Echo planar imaging (EPI) is the most widely used MRI technique used for neurosciences due to its extremely fast imaging speed and unique contrast mechanisms. EPI combined with diffusion sensitive gradient pulses provides 3D visualization of axonal fibers, which reveals the connectional anatomy of the human brain. EPI is also nearly exclusively used for functional MRI (fMRI) given its extremely high sensitivity to changes in "blood oxygen level dependent" (BOLD) contrast in different regions of the brain, revealing maps of neuronal activity. We are proposing to develop a family of highly efficient new EPI sequences for diffusion and fMRI providing several times faster imaging of the brain. This new faster imaging technique works by multiplexing several images within the single-shot echo train, to produce several images instead of a single EPI image from a each train of signals, whereas only a single image is produced in the normal EPI pulse sequence. The new Multiplexed EPI imaging sequence will largely replace the use of the original EPI sequence invented by Peter Mansfield in 1978 that to date has been used for all neuroscience and clinical brain imaging. The availability of these Multiplexed EPI techniques will give researchers and clinicians the capability of performing high angular resolution diffusion imaging (HARDI) in scan times reduced from 25 minutes to 8 or 12 minutes scans and these scan times will be more tolerable by both patients and research subjects. The multiplexed EPI can scan many times faster or instead be used to provide more images that are thinner for higher resolution and reduced artifacts. The greatly accelerated scan times of the whole brain will enable new experiments in functional MRI at 7 Tesla and 3 Tesla. The sequence will be designed, implemented and evaluated on MRI scanners operating at 3T at University of California Berkeley and San Francisco and at 7T and 10.5T at University of Minnesota. Once the Multiplexed EPI sequence is fully evaluated and optimized, it will be made into a useful tool for basic and clinical neuroscience research, and for clinical diagnostic imaging. PUBLIC HEALTH RELEVANCE: Diffusion MRI based 3D images of axonal fibers is becoming widely used method to study the anatomy of the human brain. Functional MRI (fMRI)is used to study the brain while it is performing thinking tasks and thus to map regions of brain activity. We are proposing a much faster MRI pulse sequence technology to replace existing sub-second imaging sequences used for fMRI and diffusion imaging. The new multiplexed signal encoding technology will produce several times faster multi-slice 2D images, useful for obtaining images of neuronal fibers in times under 10 minutes, supplanting the currently used slower scans that can take over 30 minutes that may often be intolerable to patients and normal people. The novel multiplexed EPI images when used for fMRI at 7T will provide much higher data sampling rates and improved statistics in functional MRI studies which will contribute to new discoveries of how the brain works. These new measurements obtained in with diffusion and fMRI will be useful for studying neurodegenerative diseases of the brain including Alzheimer's disease and for evaluating people with stroke and cerebrovascular diseases.